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1.
Eur Rev Med Pharmacol Sci ; 26(18): 6632-6641, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36196713

RESUMO

OBJECTIVE: Determining the respiratory system's mechanical properties with minimal patient effort has been an important field of investigation addressing patients unable to perform pulmonary function testing and in light of the preventive measures due to the recent pandemic. The current study aimed to present an alternative method for total respiratory resistance measurement during tidal breathing, compare it with airway resistance (Raw), measured by body plethysmography, and validate the procedure in three groups of subjects with normal, constrictive and obstructive respiratory patterns in spirometry. PATIENTS AND METHODS: We developed an alternative method of assessing total respiratory resistance during quiet breathing. After manufacturing the appropriate hardware apparatus, we applied a steady extrinsic resistance (ΔR) for 100-200 m/s during tidal breathing. Α theoretical mathematical model allowed measurement of total respiratory resistance (Rtot) during inspiration (Rin) and expiration (Rex). To validate the method, 15 individuals were enrolled and assigned to the normal, obstructive and restrictive groups based on their spirometry patterns. All groups participated in two sets of measurements, the plethysmographic and novel method. Finally, respiratory resistance measurements were compared between groups and methods. RESULTS: The method was successfully developed, and Rtot measurements were recorded in five normal subjects and in five obstructive and restrictive subjects. Mean Rin and mean Rex were 4.99 cm H2O/L/sec and 4.42 cm H2O/L/sec in the healthy, 4.87 cm H2O/L/sec, and 6.63 cm H2O/L/sec in the obstructive and 5.97 cm H2O/L/sec and 4.12 cm H2O/L/sec in the restrictive group, respectively. Rex was notably higher than Rin in the obstructive group and was positively correlated with Raw (p<0.005, r=0.47). CONCLUSIONS: This method provides the theoretical background for a plausible alternative tool for accessing a mechanical parameter of the respiratory system, which is easy to perform and requires only passive patient cooperation while enabling rough differentiation between obstructive and restrictive disorders. The model's feasibility potential in a real-life setting was studied in a small sample, and additional implementation and validation of the method in a larger population are guaranteed.


Assuntos
Resistência das Vias Respiratórias , Pulmão , Testes de Função Respiratória , Estudos de Viabilidade , Humanos , Pulmão/fisiologia , Reprodutibilidade dos Testes , Testes de Função Respiratória/métodos , Espirometria
2.
Sci Rep ; 10(1): 19325, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168856

RESUMO

A number of oocyte characteristics have been associated with fertilization, implantation and live-birth rates, albeit without reaching a consensus. This study aims to delineate possible associations between oocyte characteristics, oocyte behavior during intracytoplasmic sperm injection (ICSI), fertilization potential, and laboratory outcomes. Four-hundred and seventy-seven patients, yielding 3452 oocytes, were enrolled in this prospective observational study from 2015 to 2018. Οoplasm granularity was associated with poor embryo quality and higher probabilities of post-ICSI oocytes and embryos discarded in any developmental stage and never selected for embryo transfer or cryopreservation (p < 0.001). Both sudden or difficult ooplasm aspiration, and high or lack of resistance during ICSI were associated with either a poor Zygote-Score or fertilization failure (p < 0.001). Sudden or difficult ooplasm aspiration and high resistance during ICSI penetration were positively associated with resulting to a post-ICSI oocyte or embryo that would be selected for discard. Evaluation of oocyte characteristics and oocyte behavior during ICSI may provide early information regarding laboratory and cycle outcomes. Particularly, ooplasm granularity, and fragmentation of polar body, along with sudden or difficult ooplasm aspiration and high or lack of resistance during ICSI penetration may hinder the outcome of an ICSI cycle. The associations presented herein may contribute towards development of a grading system or a prediction model. Taking into account information on oocytes and ICSI behavior may effectively assist in enhancing IVF outcome rates.


Assuntos
Oócitos/citologia , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Coeficiente de Natalidade , Criopreservação , Transferência Embrionária , Feminino , Fertilização , Fertilização in vitro/métodos , Humanos , Infertilidade/terapia , Masculino , Indução da Ovulação , Corpos Polares/fisiologia , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Prospectivos , Resultado do Tratamento , Zona Pelúcida/fisiologia
3.
J Assist Reprod Genet ; 36(12): 2447-2457, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31786731

RESUMO

PURPOSE: To provide a global scale report on a representative sample of the clinical embryology community depicting the practice of discarding supernumerary IVF embryos. METHODS: A web-based questionnaire titled "Anonymous questionnaire on embryo disposal practices" was designed in order to ensure anonymous participation of practicing clinical embryologists around the world. RESULTS: During a data collection period of 8 months, 703 filled-in questionnaires from 65 countries were acquired. According to the data acquired, the majority of practitioners, dispose of embryos by placing them directly in a trash can strictly dedicated for embryo disposal for both fresh and frozen cycles (39% and 36.7% respectively). Moreover, 66.4% of practitioners discard the embryos separately-case by case-at different time points during the day. Over half of embryologists (54%) wait until day 6 to discard the surplus embryos, while 65.5% do not implement a specially allocated incubator space as a designated waiting area prior to disposal. The majority of 63.1% reported that this is a witnessed procedure. The vast majority of embryologists (93%) do not employ different protocols for different groups of patients. Nonetheless, 17.8% reported the request to perform a ceremony for these embryos. Assessing the embryologists' perspective, 59.5% of participants stated that the embryology practice would benefit from a universally accepted and practiced protocol. CONCLUSION(S): This study uniquely provides insight into global embryo disposal practices and trends. Results highlight the divergence between reported practices, while indicating the significance on standardization of practice, with embryologists acknowledging the need for a universally accepted protocol implementation.


Assuntos
Tomada de Decisões , Destinação do Embrião , Fertilização in vitro/tendências , Técnicas de Reprodução Assistida/tendências , Humanos , Inquéritos e Questionários
4.
J Assist Reprod Genet ; 36(6): 1049-1061, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31111304

RESUMO

PURPOSE: The present systematic review and network meta-analysis aims to uniquely bring to literature data supporting the true place of the alternative practice of day-4 embryo transfer (D4 ET) in an IVF laboratory, beyond the one-dimensional option of facilitating a highly demanding program. METHODS: A systematic search was conducted in the databases of PubMed/Medline, Embase, and Cochrane Central Library, resulting to six prospective along with nine retrospective cohort studies meeting eligibility criteria for inclusion. A comparison of D4 ET with day-2 (D2), day-3 (D3), and day-5 (D5) ET, respectively, was performed employing R statistics. RESULTS: The sourced results indicate no statistically significant difference regarding clinical pregnancy rates, and ongoing pregnancy/live birth rates stemming from the comparison of D4 with D2, D4 with D3, and D4 with D5 ET, respectively. Additionally, no statistically significant difference could be established in respect to cancelation, and miscarriage rates, following the comparison of D4 with D3 and D4 with D5 ET. Interestingly, we report statistically significant lower preterm birth rates associated with D4 ET, in contrast with D5 ET (RR, 0.19; 95% CI, 0.05-0.67; p value = 0.01). CONCLUSIONS: The aforementioned results may serve as advocates buttressing the option of D4 ET as a valid candidate in the ET decision-making process. Possible limitations of the current study are the publication bias stemming from the retrospective nature of certain included studies, along with various deviations among studies' design, referring to number and quality of transferred embryos, or different culture conditions referring to studies of previous decades.


Assuntos
Transferência Embrionária/métodos , Fertilização in vitro/métodos , Nascido Vivo/epidemiologia , Técnicas de Reprodução Assistida/tendências , Blastocisto/fisiologia , Feminino , Humanos , Metanálise em Rede , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos
5.
J Hum Nutr Diet ; 32(2): 185-197, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30378203

RESUMO

BACKGROUND: Childhood asthma is the most common respiratory disorder worldwide, being associated with increased morbidity and a decreased quality of life. Omega-3 fatty acids have anti-inflammatory and immunomodulating properties; however, their efficacy in asthma is controversial. The present study aimed to examine the efficacy of a Mediterranean diet supplemented with a high omega-3 'fatty' fish intake in Greek asthmatic children. METHODS: A single-centred, 6-month, parallel randomised controlled trial compared the consumption of a Mediterranean diet supplemented with two meals of 150 g of cooked fatty fish weekly (intervention) with the usual diet (control) with respect to pulmonary function in children (aged 5-12 years) with mild asthma. Pulmonary function was assessed using spirometry and bronchial inflammation by fractional exhaled nitric oxide analysis. RESULTS: Sixty-four children (52% male, 48% female) successfully completed the trial. Fatty fish intake increased in the intervention group from 17 g day-1 at baseline to 46 g day-1 at 6 months (P < 0.001). In the unadjusted analysis, the effect of the intervention was of borderline significance (P = 0.06, ß = -11.93; 95% confidence interval = -24.32 to 0.46). However, after adjusting for age, sex, body mass index and regular physical activity, a significant effect was observed (P = 0.04, ß = -14.15 ppb; 95% confidence interval = -27.39 to -0.91). No difference was observed for spirometry, asthma control and quality of life scores. CONCLUSIONS: A Mediterranean diet supplemented with two fatty fish meals per week might be a potential strategy for reducing airway inflammation in childhood asthma. Future robust clinical trials are warranted to replicate and corroborate these findings.


Assuntos
Asma/dietoterapia , Dieta Mediterrânea , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Produtos Pesqueiros/análise , Asma/fisiopatologia , Criança , Pré-Escolar , Feminino , Grécia , Humanos , Inflamação , Masculino , Resultado do Tratamento
6.
Biomed Res Int ; 2018: 6287507, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30112409

RESUMO

Surrogacy is an assisted reproduction-based approach in which the intended parents assign the gestation and birth to another woman called the surrogate mother. The drivers of surrogacy refer largely to infertility, medical conditions, same-sex couples' parenting, and cases of diversity regarding sexual identity and orientation. Surrogacy consists of a valid option for a variety of conditions or circumstances ranging from medical to social reasons. However, surrogacy may be associated with risks during the preimplantation, prenatal, and neonatal period. It became obvious during the exhaustive literature research that data on surrogacy and its association with factors specific to the IVF practice and the options available were not fully represented. Could it be that surrogacy management adds another level of complexity to the process from the ovarian stimulation, the subsequent IVF cycle, and the techniques employed within the IVF and the Genetic Laboratory to the fetal, perinatal, and neonatal period? This work emphasizes the risks associated with surrogacy with respect to the preimplantation embryo, the fetus, and the infant. Moreover, it further calls for larger studies reporting on surrogacy and comparing the surrogate management to that of the routine IVF patient in order to avoid suboptimal management of a surrogate cycle. This is of particular importance in light of the fact that the surrogate cycle may include not only the surrogate but also the egg donor, sperm donor, and the commissioning couple or single person.


Assuntos
Infertilidade , Cuidado Pré-Natal , Mães Substitutas , Feminino , Humanos , Lactente , Parto , Gravidez , Risco
7.
Mol Med ; 24(1): 6, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30134795

RESUMO

BACKGROUND: Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. METHODS: IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. RESULTS: We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. CONCLUSIONS: IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/metabolismo , Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Adulto , Animais , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Fator de Crescimento Insulin-Like I/genética , Interleucina-6/farmacologia , Janus Quinase 2/metabolismo , Linfócitos/imunologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos SCID , Peptídeos/farmacologia , Neoplasias da Próstata/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fator de Transcrição STAT3/metabolismo
8.
Clin Immunol ; 155(1): 33-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25173800

RESUMO

Rheumatoid arthritis (RA) synovial fibroblasts hyperexpress the mesenchymal cadherin-11, which is involved also in tumor invasion/metastasis, whereas anti-cadherin-11 therapeutics prevent and reduce experimental arthritis. To test the hypothesis that cadherin-11 is aberrantly expressed in RA peripheral blood, 100 patients (15 studied serially) and 70 healthy controls were analyzed by real-time reverse transcription-PCR. Cadherin-11 mRNA transcripts were detected in 69.2% of moderately/severely active RA, versus 31.8% of remaining patients (p=0.001), versus 17.1% of controls (p<0.0001). Notably, cadherin-11 positivity correlated significantly and independently only with established (>1year) polyarthritis (>4 swollen tender joints), by multivariate logistic regression analysis including various possible clinical/laboratory factors. Rare cells of undefined nature, detected by flow cytometry following CD45(-) enrichment, strongly expressed surface cadherin-11 (estimated 10-50cells/ml of blood) in 5/6 patients with polyarticular established disease versus 1/6 patients with early RA. Studies on the potential pathogenic role of circulating cells expressing cadherin-11 in RA are warranted.


Assuntos
Artrite Reumatoide/sangue , Caderinas/metabolismo , Regulação da Expressão Gênica/imunologia , RNA Mensageiro/metabolismo , Adulto , Idoso , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Caderinas/genética , Estudos de Casos e Controles , Linhagem Celular , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética
9.
Psychiatriki ; 25(2): 95-103, 2014.
Artigo em Grego Moderno | MEDLINE | ID: mdl-25035178

RESUMO

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, which leads to the presence of excessive daytime drowsiness. Regarding the psychological comorbidity in patients diagnosed with OSAS, previous studies focused mainly on depressive and secondarily on anxiety symptoms. Due to the lack of research data regarding the prevalence of anxiety and depressive symptoms as well as of alexithymic characteristics in patients with OSAS in Greece, the aim of the study was to record the above symptomatology in a sample of Greek OSAS patients and to investigate its relation to the respiratory parameter (Apnea-Hypopnea Index, AHI) of polysomnography. The study was conducted in a certified sleep laboratory. Thirty five randomly selected patients who attended the laboratory with symptoms of daytime drowsiness, fatigue, disrupted sleep and snoring, were examined for anxiety, depression and alexithymia using the Spielberger Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Toronto Alexithymia Scale (TAS-20), respectively, 24 hours prior to being submitted to polysomnography. All 35 patients met the inclusion criteria of the study (age≤75 years, no other chronic diseases and no history of major psychiatric disorders). Six patients did not meet the diagnostic criteria for OSAS and were thus used as the control group of the study. A high prevalence of anxiety (41.4%) and depressive (55.2%) symptoms and of alexithymic characteristics (41.4%) was observed in OSAS patients. Although the control group showed a higher prevalence of anxiety (66.7%) and depressive (83.3%) symptoms, there were no differences between the two groups (STAI: t=-0.927, p=0.360, BDI: t=-1.537, p=0.134, TAS-20: t=0.196, p=0.846). With regard to severity, no differences were observed between control, mild, moderate and severe OSAS subgroups (STAI: F=0.583, p=0.660, BDI: F=0.829, p=0.488, TAS-20: F=0.987, p=0.412). Females scored higher on the BDI and on the STAI compared to males (STAI: t=-2.38, p=0.039, BDI: t=-3.59, p=0.01). Finally, no correlation was observed between psychometric scores and AHI (Pearson correlation p>0.05). The study confirms the high prevalence of anxiety and depressive symptoms which has been found in previous studies. Furthermore, we found a high prevalence of alexithymic characteristics, a factor that has not been investigated previously and which is positively correlated with anxiety symptoms. The coexistence of alexithymic characteristics may further complicate the clinical manifestations of OSAS due to the fact that patients with alexithymia typically have difficulty in indentifying and describing their underlying psychological symptomatology and, moreover, tend to exhibit more, and often atypical, physical symptoms. In conclusion, the study supports the presence of a high degree of psychological burden in patients diagnosed with OSAS, regardless of the severity of their symptoms, as determined by the AHI. This comorbidity should be taken into consideration during the clinical assessment of OSAS and for the treatment planning.


Assuntos
Efeitos Psicossociais da Doença , Apneia Obstrutiva do Sono/psicologia , Adulto , Sintomas Afetivos/etiologia , Sintomas Afetivos/psicologia , Ansiedade/etiologia , Ansiedade/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Polissonografia , Apneia Obstrutiva do Sono/complicações
10.
Obes Rev ; 15(6): 487-503, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24612276

RESUMO

Obesity is a major epidemic of our time and is associated with diseases such as metabolic syndrome, type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Although weight loss drugs, when accompanied by diet and exercise, could be a very helpful medical tool in treating obese or overweight patients, their usefulness has been questioned due to the complexity of this type of medication, which regards a plethora of issues such as efficacy and safety of the drug and also risks and benefits among different patients. In general, obesity drugs that target peripheral pathophysiological mechanisms can be divided into two main categories. The first category includes anti-obesity agents able to reduce or limit energy absorption, such as pancreatic lipase and microsomal triglyceride transfer protein inhibitors. The second category consists of a heterogeneous group of compounds aiming to decrease fat mass by increasing energy expenditure or by redistributing adipose tissue. Angiogenesis inhibitors, beta-3 receptor agonists, sirtuin-I activators, diazoxide and other molecules belong to this group. The glucagon-like peptide-1 receptor agonists consist the third category of peripheral anti-obesity agents discussed therein. This review aims to provide a general overview of the molecules and substances that are already or could potentially be used as peripheral anti-obesity drugs, the molecular mechanisms by which they act, as well as their current stage of development, production and/or availability.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Aciltransferases/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Inibidores da Angiogênese , Proteínas de Transporte/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Metabolismo Energético/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Lipase/antagonistas & inibidores , Receptores de Glucagon/agonistas , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose , Receptores beta dos Hormônios Tireóideos/agonistas
11.
J Musculoskelet Neuronal Interact ; 13(2): 133-46, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23728100

RESUMO

It is well established that physical exercise modulates the function of many physiological systems, such as the musculoskeletal, the cardiovascular and the nervous system, by inducing various adaptations to the increased mechanical load and/or metabolic stress of exercise. Many of these changes occur through epigenetic alterations to DNA, such as histone modifications, DNA methylations, expression of microRNAs and changes of the chromatin structure. All these epigenetic alterations may have clinical relevance, thus playing an important role in the prevention and confrontation of neurophysiological disorders, metabolic syndrome, cardiovascular diseases and cancer. Herein we review the known epigenetic modifications induced by physical exercise in various physiological systems and pathologies, and discuss their potential clinical implications.


Assuntos
Epigênese Genética/fisiologia , Exercício Físico/fisiologia , Expressão Gênica/fisiologia , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Fenômenos Fisiológicos Cardiovasculares , Sistema Nervoso Central/fisiologia , Humanos , Inflamação/genética , Inflamação/fisiopatologia , Neoplasias/genética , Neoplasias/fisiopatologia
12.
J BUON ; 17(3): 605-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23033312

RESUMO

In the 17th century, iatromechanists based to the solidist theory for the lymphatic system and lymph established a new speculation for the essential role of lymph in oncogenesis, while animists gave their own views in relation to the cause of cancer. Gradually, with the rise of pathological anatomy, new more rational theories have emerged.


Assuntos
Transformação Celular Neoplásica , Linfa/fisiologia , Humanos
13.
Trends Endocrinol Metab ; 23(12): 628-36, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22902904

RESUMO

Wnt signaling pathways play a key role in cardiac development, angiogenesis, and cardiac hypertrophy; emerging evidence suggests that they are also involved in the pathophysiology of atherosclerosis. Specifically, an important role for Wnts has been described in the regulation of endothelial inflammation, vascular calcification, and mesenchymal stem cell differentiation. Wnt signaling also induces monocyte adhesion to endothelial cells and is crucial for the regulation of vascular smooth-muscle cell (VSMC) behavior. We discuss how the Wnt pathways are implicated in vascular biology and outline the role of Wnt signaling in atherosclerosis. Dissecting Wnt pathways involved in atherogenesis and cardiovascular disease may provide crucial insights into novel mechanisms with therapeutic potential for atherosclerosis.


Assuntos
Aterosclerose/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Calcinose/etiologia , Cardiomegalia/metabolismo , Adesão Celular/fisiologia , Humanos , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/fisiopatologia , Transdução de Sinais/fisiologia , Doenças Vasculares/etiologia , Proteínas Wnt/fisiologia
14.
In Vivo ; 26(1): 75-86, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22210719

RESUMO

AIM: The aim of this study was to evaluate whether the neoadjuvant use of the dexamethasone (DEX) plus octreotide (OCT) regimen can improve the direct anticancer effects of docetaxel (DOC) in the TRAMP-C1 prostate cancer model. MATERIALS AND METHODS: TRAMP-C1 cells were first characterized for the expression of SSTR1-5 and then were inoculated onto the femur of C57Bl mice. Investigation protocols employed TRAMP-C1 cell proliferation and invasion assays, analysis of radiographic images of the bone lesions and overall survival of the diseased animals. RESULTS: The triple combination treatment scheme showed significant anticancer effects, in both proliferation and invasion assays, compared to any single agent treatment scheme. DOC treatment following the neoadjuvant administration of DEX plus OCT regimen improved significantly the anticancer effects both on the grading of the bone lesions and on the overall survival of the diseased animals. CONCLUSION: Our data suggest that the neoadjuvant administration of DEX plus OCT regimen can improve the anticancer effects of DOC on the TRAMP-C1 model.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/farmacologia , Octreotida/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Taxoides/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Docetaxel , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Octreotida/administração & dosagem , Osteoprotegerina/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ligante RANK/sangue , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxoides/administração & dosagem
15.
In Vivo ; 26(1): 119-27, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22210725

RESUMO

BACKGROUND: The KISS1/KISS1R system has been implicated in the physiology of reproduction and many studies have documented the stimulatory effect of kisspeptin on Gonadotropin-releasing Hormone (GnRH) and gonadotropin secretion. In addition, the KISS1/KISS1R system has been implicated in several pathophysiological processes, including cancer. MATERIALS AND METHODS: We examined the pattern of KISS1 and KISS1R expression in eutopic and ectopic endometrium tissues which were obtained from 24 women suffering from endometriosis and 16 control women who underwent laparoscopic excision for other benign gynecological diseases. RESULTS: Significant KISS1R expression was detected in 10 out of the 24 samples of eutopic endometrial biopsies of women suffering from endometriosis, while their matched biopsies of ectopic endometrial lesions did not reveal any KISS1R expression. KISS1R expression was not detected in the endometrial biopsies of control women. In addition, KISS1 expression was not detected in practically any the endometrial tissues of either control women or women with endometriosis. CONCLUSION: The expression of KISS1R in 10/24 samples of human endometrial biopsies of women suffering from endometriosis and the loss of its expression in the samples of matched ectopic endometrial tissues, suggests that the KISS1/KISS1R system may play a role in the pathophysiology of endometriosis only for a particular group of patients. Since KISS1 is not expressed by the endometrium and endometriotic tissue, it is conceivable that the activation of KISS1R in this particular group is mediated by KISS1 expression by non-endometrial tissues (endocrine action).


Assuntos
Coristoma/genética , Endometriose/genética , Endométrio/metabolismo , Perfilação da Expressão Gênica , Kisspeptinas/genética , Receptores Acoplados a Proteínas G/genética , Adulto , Biópsia , Endometriose/patologia , Endométrio/patologia , Feminino , Humanos , Receptores de Kisspeptina-1 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
16.
In Vivo ; 25(3): 343-54, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21576407

RESUMO

The Kiss-1 gene encodes a secreted protein that is proteolytically cleaved to produce a number of structurally related peptides, with high interspecies conservation, globally termed kisspeptins. The original niche for the role of kisspeptin in human physiology is derived from cancer biology, with the loss of Kiss-1 expression being associated with poor prognosis in several malignancies. However, kisspeptin has recently emerged as a fundamental player in the field of reproductive biology. Genetic analysis of large consanguineous pedigrees by two independent groups led to the association of inactivating mutations of GPR54, the receptor which mediates kisspeptin action, with idiopathic hypogonadotropic hypogonadism. In the present paper the most salient aspects of the multifaceted role of kisspeptin in the reproductive system are reviewed, including the association of kisspeptin with the gonadal steroid feedback loop and the triggering of puberty onset.


Assuntos
Receptores Acoplados a Proteínas G/metabolismo , Reprodução/fisiologia , Proteínas Supressoras de Tumor/metabolismo , Animais , Encéfalo/metabolismo , Gônadas/metabolismo , Humanos , Kisspeptinas , Mutação/genética , Puberdade/genética , Puberdade/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Kisspeptina-1 , Proteínas Supressoras de Tumor/genética
17.
Lung Cancer ; 73(1): 51-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21111510

RESUMO

PURPOSE: To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of obvious urothelial metastases. PATIENTS AND METHODS: 150 patients with small (SCLC) and non-small cell lung cancer (NSCLC) of all stages and 3 control groups were prospectively studied. Immunocytochemical study (cytokeratins 7-20, TTF1) in all positive urine specimens and chemokine profile (CXCR4, CCL21) study of the primary tumor in selected positive patients was performed. In experimental study, C57Bl/6 BALB/C mice injected with LLC lung and 4T1 mammary cancer cells were used for the detection of positive urine cytology. RESULTS: 11% of patients with NSCLC, 7% of patients with SCLC and none of the control group had positive urine cytology. In NSCLC, metastatic disease and high tumor burden positively correlated (p=0.01 and 0.03 respectively) with the phenomenon. In SCLC, correlation with extensive disease and multiple metastatic sites (p=0.02 and 0.04 respectively) was found. No correlation was found in either group with: age, gender, histology, performance status, line of chemotherapy, previous platinum-based chemotherapy, adrenal metastases, renal function, abnormal urinary sediment, response to chemotherapy and overall survival (p=0.9). Distinctive chemokine expression was identified in positive patients studied and was not observed in negative patients (×2 p=0.008). In the experimental study, only the LLC lung cancer cells were detected in the urine cytology of mice. CONCLUSION: This phenomenon, carrying undefined pathophysiological mechanisms, seems to characterize only patients with metastatic/extensive disease and high tumor burden. Further studies are needed to validate our preliminary chemokine expression results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/urina , Neoplasias Pulmonares/urina , Carcinoma de Pequenas Células do Pulmão/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Lewis/urina , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Quimiocina CCL21/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/urina , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transplante de Neoplasias , Receptores CXCR4/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Transplante Heterólogo , Neoplasias Urológicas/secundário
18.
Horm Metab Res ; 42(8): 543-52, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20419622

RESUMO

Endocrine disruption represents one of the most controversial environmental issues of our époque. So far, many substances, both natural and artificial, have been recognized to interfere with endocrine signaling pathways. In intact laboratory animals, this interaction has been documented to generate adverse health outcomes by impairing normal functions. With regard to humans, evidence is limited and inconsistent to clearly establish a causal inference, however, accumulating data incriminate endocrine disrupting chemicals to reproductive disorders and disturbed thyroid homeostasis. Recently, as a result of animal models and preliminary human studies, a new area of interest has arisen concerning the implication of endocrine disruptors in the etiology of obesity and diabetes, the two major, life-threatening, epidemics of modern world. This article reviews the evidence linking endocrine disrupting chemicals to a broad spectrum of clinical perturbations from reproduction and thyroid to metabolic regulation.


Assuntos
Disruptores Endócrinos/toxicidade , Sistema Endócrino/efeitos dos fármacos , Animais , Doença , Poluentes Ambientais/toxicidade , Feminino , Genitália Feminina/efeitos dos fármacos , Genitália Masculina/efeitos dos fármacos , Humanos , Masculino
19.
Curr Opin Cell Biol ; 22(1): 81-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20022232

RESUMO

The asymmetric cell division process is required for cellular differentiation and embryonic development. Recent evidence obtained in Drosophila and C. elegans suggest that this process occurs by non-equivalent distribution of proteins or mRNA (intrinsic factors) to daughter cells, or by their differential exposure to cell extrinsic factors. In contrast, haploid fission yeast sister cells developmentally differ by inheriting sister chromatids that are differentiated by epigenetic means. Specifically, the act of DNA replication at the mating-type locus in yeast switches it's alternate alleles only in one specific member of chromosome 2 sister chromatids in nearly every chromosome replication cycle. To employ this kind of mechanism for cellular differentiation, strictly based on Watson-Crick structure of DNA in diploid organism, selective segregation mechanism is required to coordinate distribution of potentially differentiated sister chromatids to daughter cells. Genetic evidence to this postulate was fortuitously provided by the analysis of mitotic recombinants of chromosome 7 in mouse cells. Remarkably, the biased segregation occurs in some cell types but not in others and the process seems to be chromosome-specific. This review summarizes the discovery of selective chromatid segregation phenomenon and it suggests that such a process of Somatic Sister chromatid Imprinting and Selective chromatid Segregation (SSIS model) might explain development in eukaryotes, such as that of the body axis left-right visceral organs laterality specification in mice.


Assuntos
Padronização Corporal/fisiologia , Diferenciação Celular/fisiologia , Cromátides/fisiologia , Segregação de Cromossomos , Mitose , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/crescimento & desenvolvimento , Replicação do DNA , Drosophila melanogaster/citologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Dineínas/genética , Dineínas/metabolismo , Camundongos , Fuso Acromático/metabolismo
20.
In Vivo ; 23(5): 859-65, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19779124

RESUMO

Muscular adaptation which occurs following eccentric exercise-induced muscle damage has been associated with changes in the mechanical properties of muscle manifested as a shift in the length-tension relationship towards longer muscle lengths. However, it is not clear whether this shift is a long term adaptation to eccentric exercise. The purpose of this study was to investigate functional adaptations to skeletal muscle damage in humans, tracking such responses several days into muscle recovery. Ten healthy young men performed an eccentric exercise protocol involving the quadriceps muscle and functional measurements were performed before and on days 1, 2, 5, 8, 12 and 16 post-exercise. Blood samples were also withdrawn before and at 6 h, and 2 days, 5 days and 16 days post-exercise. The exercise protocol resulted in muscle damage, indicated by changes in clinical markers including increased serum creatine kinase activity and muscle soreness compared to pre-exercise levels (p<0.05-0.001). An acute, but not sustained shift in the quadriceps isokinetic and isometric angle-torque curves towards longer muscle lengths was observed post-exercise (p<0.05). It was speculated that the functional adaptations following eccentric exercise might be affected by the short resting and functional length of the quadriceps muscle, relative to its optimum. More studies are needed to confirm the hypothesis that a sustained shift in the muscle's length-tension relationship, as an adaptation after lengthening contraction-induced damage, is muscle specific.


Assuntos
Adaptação Fisiológica/fisiologia , Exercício Físico/fisiologia , Músculo Quadríceps/fisiologia , Adulto , Fenômenos Biomecânicos/fisiologia , Creatina Quinase/sangue , Humanos , Contração Isométrica , Perna (Membro)/fisiologia , Masculino , Fadiga Muscular/fisiologia , Músculo Quadríceps/lesões , Torque
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